POS0290 THE EFFECTS OF TREATMENT RESPONSE AND RISK FACTOR TO INHIBIT THE CLINICAL RESPONSE IN PATIENTS WITH DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS TREATED WITH IL-6 RECEPTOR INHIBITOR, ABATACEPT AND JAK INHIBITOR
Authors: S. Anno, T. Okano, K. Mandai, K. Orita, Y. Yamada, K. Mamoto, T. Iida, M. Tada, K. Inui, T. Koike, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2022)

Background Recently, the disease activity of rheumatoid arthritis (RA) was improved due to the ‘treat-to-target’ strategy. However, some patients remain various symptoms despite recommended treatment was performed. Then, the term of ‘difficult-to-treat RA (D2TRA)’ is widely recognized. It is unknown how the difference of type of biological disease-modifying anti rheumatic dugs (bDMARDs)/Janus kinase inhibitor (JAKi) will affect clinical efficacy in patients with D2TRA. Moreover, the risk factor to inhibit the clinical response in patients with D2TRA is unknown. Objectives The aim of this study was to evaluate the treatment response in patients with D2TRA who were treated with interleukin 6 receptor inhibitor (IL-6Ri), abatacept and JAKi. Methods This study used the multicenter database included 673 RA patients treated with bDMARDs/JAKi (tocilizumab 240, sarilumab 67, abatacept 146, tofacitinib 101, baricitinib 83, upadacitinib 20, peficitinib 14, filgotinib 2). Two hundred forty-two patients were treated as first line bDMARDs/JAKi (IL-6Ri 117, abatacept 63, JAKi 62), 211 patients were treated as second line bDMARDs/JAKi (IL-6Ri 117, abatacept 37, JAKi 57), 220 patients were treated as third and more bDMARDs/JAKi. In these 220 patients, 82 patients did not meet D2TRA criteria (IL-6Ri 42, abatacept 15, JAKi 25) and 138 patients met D2TRA criteria (IL-6Ri 31, abatacept 31, JAKi 76). In all patients, we analyzed 138 patients with D2TRA (113 female, mean age was 63.1 ± 13.7 years). Drug retention rate and effectiveness of bDMARDs/JAKi in patients with D2TRA were evaluated for 24 weeks. Multivariate linear regression analysis was performed to clarify the risk factors to inhibit the clinical response. Results Drug retention rate of patients with D2TRA at 24 weeks was 67.7% in IL-6Ri group, 74.2% in abatacept group, 61.8% in JAKi group. Drug retention rate in patients with D2TRA was not different between groups (IL-6Ri vs abatacept: p=0.86, IL-6Ri vs JAKi group: p=0.39, abatacept vs JAKi group: p=0.33). DAS28-CRP at 4, 12, 24 weeks decreased in all group (Figure 1). Abatacept showed lower improvement ratio of DAS28-CRP at 24 weeks compared to IL-6Ri group (IL-6Ri vs abatacept: p&lt;0.01, IL-6Ri vs JAKi: p=0.1, abatacept vs JAKi: p=0.07). Good responder (defined as decrease in DAS28-CRP score &gt; 1.2 with a score &lt; 3.2) was 52.4% patients in IL-6Ri, 17.4% patients in abatacept, 29.8% patients in JAKi. SDAI and CDAI at 4, 12, 24 weeks decreased in all group (Figure 1). There were no diferences between the groups in improvement ratio of SDAI (IL-6Ri vs abatacept: p=0.11, IL-6Ri vs JAKi: p=0.81, abatacept vs JAKi: p=0.08) and CDAI (IL-6Ri vs abatacept: p=0.31, IL-6Ri vs JAKi: p=0.82, abatacept vs JAKi: p=0.13) at 24 weeks. HAQ was 1.42, 1.15, 1.39 at baseline, 1.27, 1.07, 1.22 at 4 weeks, 1.17, 1.07, 1.17 at 12 weeks, 1.26, 1.06, 1.14 at 24 weeks in IL-6Ri group, abatacept and JAKi, respectively. Multivariate linear regression analysis revealed that high HAQ (β=0.28, p=0.02) and high dosage of glucocorticoid (β=0.67, p&lt;0.01) inhibited the improvement of DAS28-CRP. Type of bDMARDs/JAKi (β=-0.09, p=0.36) did not affect the DAS28-CRP improvement for 24 weeks. Table 1. Multivariate linear regression analysis of risk factor to inhibit the clinical response in patients with D2TRA. β 95% CI p Age (years) -0.037 -0.025, 0.017 0.74 male -0.047 -0.788, 0.486 0.64 Disease durations (years) -0.048 -0.028, 0.017 0.63 RF (IU/ml) -0.082 -0.0004, 0.0002 0.41 Anti CCP antibody (U/ml) 0.111 -0.0005, 0.002 0.26 DAS28-CRP -0.063 -0.265, 0.142 0.55 HAQ 0.279 0.059, 0.717 0.02 MTX (mg/day) 0.136 -0.018, 0.081 0.21 Glucocorticoid dose (mg/day) 0.669 0.174, 0.324 &lt; 0.01 Type of bDMARDs/JAKi -0.088 -0.415, 0.151 0.36 Conclusion Drug retention rate and clinical efficacy of D2TRA patients were not different among IL-6Ri, abatacept and JAKi. DT2RA patient with functional disorder and high dosage of glucocorticoid were risk factor to inhibit the clinical response. Disclosure of Interests None declared